1, 7-Dimethylnaphthalene was obtained by the dehydrogenation of ethyl hinokiate, C₄H₂₁COOC₂H₅, with selenium. The same dehydrogenation of hinokilol, C₁₄H₂₁CH₂OH, yielded 1, 6, 7-trimethylnaphthalene. These results revealed that hinokiic acid is a tricyclic compound possessing a naphthalene nucleus substituted with two methyl groups in 1- and 7-positions and a carboxyl group in the 6-position, and another ring which is unstable to dehydrogenation. The two carbon atoms that liberated during dehydrogenation seem to have combined as a quaternary group with the nucleus, such as gem or angl type side-chain. Bicycloisohinokiic acid, C₁₄H₂₁COOH, the oily bicyclic product obtained on treating hinokiic acid with 50% sulfuric acid, yielded 1, 7-dimethylnaphthalene by dehydrogenation. Bicycloisohinokiic acid was found to contain a conjugated double bond which was identified by bromine absorption, catalytic hydrogenation, and addition of maleic anhydride.

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Oxidation of bicycloisohinokiic acid with potassium permanganate in alkaline solution yielded an oily dicarboxylic acid, in which one of the carboxyl group was found to be quaternary by titration. The p-bromophenacyl ester, m.p. 134-135°, of this acid was found to be identical with the derivative prepared from β-ionone via bicyclodehydrofarnesenic acid. From the results of oxidation, it has been proved that bicycloisohinokiic acid is 1, 1, 7, 10-tetramethyl-Δ^{5, 7}-dihydronaphthalene-6-carboxylic acid.

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Ozonic oxidation of hinokiic acid yielded a diketomonocarboxylic acid, C₁₁H₁₈(COCH₃)COCOOH, and a ketonic substance, C₁₃H₂₀O, as a by-product. On further oxidation of the diketonic acid, following seven compounds were obtained: Ketonic aldehyde, C₁₁H₁₈(COCH₃)CHO; ketonic acid, C₁₁H₁₈(COCH₃)COOH and its methyl ester; unsaturated ketonic ester C₁₄H₁₉O(_??_₁)COOCH₃; keto-dicarboxylic ester, C₁₁H₁₈(COOH)COCOOCH₃; dicarboxylic acid, C₁₀H₁₆(COOH)₂, and its monomethyl ester; crystalline dicarboxylic acid, C₁₁H₁₈(COOH)₂, and its dimethyl ester; and dicarboxylic acid, C₉H₁₆(COOH)₂ (1, 1, 3-trimethylcyclohexane-2, 3-dicarboxylic acid), and its methyl ester. From these results, it has become clear that the double bond in hinokiic acid is situated between the 6- and 7-positions of the hydronaphthalene ring, and that the bridged bond between 5- and 9-positions form the unstable cyclopropane ring condensed to the saturated six-membered ring.

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Alkaline permanganate oxidation of hinokiic acid yielded a crystalline dicarboxylic acid, C₁₁H₁₈(COOH)₂, and a ketonic acid, C₁₁H₁₈(COCH₃)COOH. These acids, and the products obtained on further oxidative degradation, proved identical with the products of ozonolysis of hinokiic acid. From the results of experiments as outlined in these papers, the author proposed a constitution formula of hinokiic acid (cf. Figs.).

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It has already been reported that the thermal reaction of safrole or methyleugenol with acid amide, in the presence of phosphoryl chloride, resulted in the formation of an isoquinoline derivative. The use of aliphatic or aromatic aldoxime, in place of acid amide, was found to give 1-substituted 3-methyl-6, 7-dimethoxy (or methylenedioxy)-3, 4-dihydroisoquinoline. The isoquinoline derivative was obtained in approximately 30% yield when 1 mole each of allylbenzene and aldoxime mixture was allowed to react in an ice bath, allowed to stand for some time at a room temperature, then allowed to boil gently in a water or an oil bath, decomposed with ice water, impurities such as safrole and methyleugenol removed, and the basic substance collected. The aldoximes used were acetaldoxime, benzaldoxime, anisaldoxime, veratraldoxime, and piperonaldoxime. By this means, 3, 4-dihydroneupaverine could be obtained by a single process.

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Amstutz, et al. assumed that the substance obtained on the reduction of 2, 8-dinitro-thiaxanthone 5-dioxide with zinc powder and acetic acid was 2, 8-diaminothiaxanthene 5-dioxide (I) but the reëxamination of this reaction revealed that the reduction product was not (I) but 2, 8-diaminothiaxanthenol 5-dioxide (II), since the reduction of (II) with hydriodic acid and red phosphorus yielded (I). (I) can also be obtained by the application of fuming sulfuric acid on 3, 3′-diaminodiphenylmethane, or by the sulfonation of 3, 3′-diacetaminodiphenylmethane with chlorosulfonic acid followed by hydrolysis.

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Application of sodium polysulfide to 2, 2′-dichloro-5, 5′-dinitrodiphenylmethane yields 2, 8-dinitrothiaxanthene whose reduction gives 2, 8-diaminothiaxanthene, and oxidation, 2, 8-dinitrothiaxanthone 5-dioxide.

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Antibacterial activity was tested with 52 kinds of organic compounds which virtually failed to show any growth inhibition against Escherichia coli communior. The following compounds were found to completely inhibit the growth of Micrococcus pyo-genes var. aureus 209 P at concentrations above 80, 000: Thymoquinone, 1, 4-naphthoquinone, 1, 4-naphthoquinone bis (guanylhydrazone nitrate), p-nitrothymol, 2-chloro-3-methyl-4-thiocyano-6-isopropylphenol, and 2-chloro-4-acetylthymol. p-Nitro- and 2-chloro-4-acetylthymol were able to inhibit growth at 320, 000 dilution and 2-chloro-3-methyl-4-thiocyano-6-isopropylphenol at 640, 000 dilution. The following compounds were found to inhibit the growth of Bacillus subtilis at over 80, 000 dilution: p-Nitrothymol, 2-chloro-3-methyl-4-thiocyano-6-isopropylphenol, 2-chloro-4-acetylthymol, and 3-methyl-4-thiocyano-6-isopropylphenol. Of these compounds, the second-named was able to completely inhibit the growth of this microörganism at 640, 000 dilution.

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The phenazine synthesis of Wohl-Aue was modified to utilize m-nitroanisole and aniline by which 1-methoxyphenazine, 2-methoxyphenazine 10-N-oxide, and 1-methoxyphenazine 5-N-oxide were obtained in 7:2:1 ratio. The use of m-anisidine and nitrobenzene gave 1-methoxyphenazine and 2-methoxyphenazine 5-N-oxide in 2:1 ratio. These results have shown that the Wohl-Aue reaction resulted in the condensation taking place more readily at the ortho position to the methoxyl group than at the para position. The product obtained by the condensation at the para position was found to be the mono-N-oxide compound.

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A method was devised whereby a minute amount of α-crocin contained in the crocus could be rapidly and correctly determined by the use of the Leitz-Rouy photometer. One mg. of pure α-crocin was dissolved in water to make 100cc. of a solution, placed in an absorption tube by the usual method, and a standard graph was drawn up from the indications of the galvanometer, using 415mμ filter. Next, 0.05% solution of potassium dichromate was prepared and its standard graph prepared. It was found that the standard curve of the dichromate solution above 50γ concentration was found to be parallel to that of α-crocin curve (cf. Fig. I). It follows, therefore, that the standard curve prepared with potassium dichromate solution could be used in place of α-crocin. The relationship between the two could be calculated from the following equation:
α-Crocin (in γ)=K₂Cr₂O₇(inγ)/50+0.7
where 0.7 denotes a constant when the Leitz-Rouy photometer is employed with a filter of 415mμ. An aqueous extract of crocus powder is used for the determination of α-crocin.

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Anemarrhena asphodeloides Bunge is a plant of the Liliaceae family growing wild in China where its bulb has been used for the past two centuries as “Ti-mu” as home remedies for diuretic, expectorant, antitussive, and others. The plant was imported into Japan some 300 years ago and used as home remedies. A kind of saponin, m.p. 278-280°, was recently isolated from its bulb. The hydrolysis of the crude saponin with hydrochloric acid yielded two kinds of steroidal sapogenins of m.p. 198° and 242-243°. The former was identified as the chief component and was found identical with sarsa-sapogenin. The latter was assumed to correspond to formula C₂₇H₄₂O₄or C₂₇H₄₄O₄, but due to the minute amount available, no further examinations were made.

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Antitubercular tests were made with cold extract of 116 kinds of domestic lichens digested with 70% alcohol. Fairly strong antibacterial actions were found in the following: Cetraria nivalis Ach., Cladonia sylvatica (L.) Hoffm., C. pseudostellata Asahina, C. Floerkeana (Fr.) Sommerfelt, Cornicularia Satoana (Gyel.) Asahina, Haematomma ventosum (L.) Mass., Evernia mesomorpha f. esorediosa Mull. Arg., Phylliscum japonicum A. Zahlbr., Sticta Mougeotiana Del., Stereocaulon paschale Ach., Usnea ceratinella Wain, and Usnea Montis-Fuji Motyka.

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The method of preparing ketolactone (XI) from diethyl [3-ketocyclohexen-(1)-yl]-methylmalonate (I), the same starting material as used by Paranjape, was further examined and a new method of preparation was found. In order to change the ketone group to hydroxyl, without disturbing the double bond, the Meerwein-Ponndorf reduction of (I) was carried out by which α-[cyclohexadien-(1, 3)-yl]-propionic acid (II) was obtained. Attempt to saturate the double bond without disturbing the ketone group was made by catalytic reduction, using palladium-carbon, by which diethyl (3-keto-cyclohexyl)-methylmalonate (V) was obtained. Its saponification and low-pressure distillation yielded α-(3-ketocyclohexyl)-propionic acid (VIII) which provided, by the action of two moles of bromine, the lactone of α-(2-hydroxy-3-keto-4-bromocyclohexyl)-propionic acid (X) as crystals of m.p. 113° (decomp.). Reduction of (X) with palladium-calcium carbonate as a catalyst yielded the same ketolactone (XI) as obtained in the previous experiments.

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Condensation of hexen-(2)-ol-(4) with anisole or o-cresol methylether, with conc. sulfuric acid as the condensation agent, gave, as an intermediate, p-methoxy- or m-methyl-p-methoxy-phenylhexene, in over 70% yield. By the stepwise addition of anisole or o-cresol methylether, it was found to give a better yield of 3, 4-(p, p′-dimethoxydiphenyl)- or 3, 4-(m, m′-dimethyl-p, p′-dimethoxydiphenyl)-hexane than by the one-step synthesis.

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The method of preparing 3, 4-diphenylhexane compounds by the condensation of alkylbuten-(2)-ol-(4) and benzene derivatives, with conc. sulfuric acid as a condensation agent, was designated the allylalcohol method. Distinguishing the two methods available, the one-step method was designated as A method, and the stepwise synthesis as B method. Asymmetric compounds possessing different alkyl groups, of the type Ar-CH(R)-CH(R′ differ), such as 3, 4-(p, p′-dimethoxydiphenyl)-pentane, -heptane, and -octane were prepared by the two methods, A and B. It was confirmed that these compounds had not undergone allyl rearrangement by the direct comparison with the same compounds prepared by still another method.

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The asymmetric 3, 4-diphenylhexane derivatives, such as 3, 4-(m-methyl-p, p-dimeth-oxydiphenyl)-hexane belonging to the Ar-CH(Et)-Ar′ type, where the two aryl groups differ, and 3, 4-(m-methyl-p, p′-dimethoxydiphenyl)-pentane and -heptane, belonging to the Ar-CH(Et)-CH(R)-Ar′, where both alkyl and aryl groups differ, could not be prepared by A method but were prepared by the B method, the allyl alcohol method. However, these compounds were all syrupy oil and were therefore led to their dibenzoates by demethylation and the Schotten-Baumann reaction. Dibenzoate of the hexane compound, m.p. 175-178°; dibenzoate of the pentane compound, m.p. 179-181°; and dibenzoate of the heptane compound, m.p. 180-182°.

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Allylbenzene was prepared by the condensation of allyl alcohol and benzene, with 92% sulfuric acid as the condensation agent, as in the case of hydrofluoric acid as the agent. Allylbenzene was confirmed as its tribromide of m.p. 124-125°. This method was utilized in the preparation of various asymmetric 3, 4-diphenylhexane compounds by the condensation of alkylbuten-2-ol-4 in place of allyl alcohol, and anisole and o-cresol methyl ether, in place of benzene. The occurrence of allyl rearrangement in the condensation of alkybuten-2-ol-4 and anisole, with conc. sulfuric acid as the condensation agent, was examined by the ozonic oxidation of the intermediates, p-methoxy-phenylalkylbutene, with subsequent examination of the Rf value by the paper chromato-graphy of the fatty acids obtained by the ozonolysis. From the paper chromatograms it was ascertained that acetic acid alone was formed when the alkyl was methyl in alkylbuten-2-ol-4 acetic and propionic acids when alkyl was ethyl, acetic and butyric acids in the case of propyl, and acetic and valeric acids in the case of butyl. The quantitative estimation could not be made but it was assumed, from the width of the chromatographic pattern, that acids other than acetic acid were formed only in a small quantity. It follows, therefore, that the intermediates were chiefly that had not undergone allyl rearrangement, only a minute amount of those that had undergone rear-rangement being occluded.

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4-(3′-Methoxyphenoxy)-phenylacetic acid (III) was prepared by the following two methods. The first method was the hydrolysis of ethyl 4-(3′-methoxyphenoxy)-phenylacetate (II), obtained by the Ullmann condensation of ethyl p-bromophenylacetate (I) and resorcinol monomethyl ether, the yield being 3.3-6.7% of the theoretical amount. The second method was the Willgerodt reaction of 3′-methoxy-4-acetyldiphenyl ether (V) obtained by the Ullmann condensation of p-bromoacetophenone (IV) and resorcinol mono-methyl ether. In this Willgerodt reaction, methods of reacting ammonia water and sulfur in pyridine base solvent, in a sealed tube or in the autoclave, or using ammonium polysulfide, were attempted but in all these cases, corresponding acid amide could not be obtained and only thioamide (VI) was obtained. Hydrolysis of the thioamide thus obtained yielded the objective acid (III), m.p. 81-82°, as crystallized from carbon tetrachloride. This acid was completely identical with the acid obtained by the Ullmann condensation but the yield was very poor in every case, being 3-10% of the theory when using a sealed tube, 3.9% in an autoclave, and 5.6% when using polysulfide.

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To determine the intensity of the violet indigo fluorescence produced from dehydro ascorbic acid and o-phenylenediamine, a fluorophotometer was devised. Practicability of this apparatus was confirmed by the parallelism between the concentration of the solution and intensity of photoelectric current, using riboflavin and thiochrome. The features of this apparatus are the avoidance of the use of mercury lamp, use of nitrofurazone compounds for the interception of the ultraviolet rays, use of individual voltage stabilizers for the light source and amplifiers to offset the variation of electric current at the source, and the increase in the intensity and providing for variability by the use of 10-step variable resistor.

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The specificity and sensitivity of the fluorescence reactions that occur between dehydroascorbic acid, oxidation-type reductone, and α-keto acid, with o-phenylenediamine were utilized for detection in paper chromatography. Chromatograms of ascorbic acid, its allied compounds, and of α-keto acids were prepared and their Rf values were determined. As a result, it was found that the present reaction was specific in detect-ing dehydroascorbic acid, which was undetectable by the existing methods, 5γ of this acid being detected. It was confirmed that the use of thiourea as the stabilizing agent for ascorbic acid chromatography increased the detection limit two to four times, and that the Rf value of 2, 3-diketo-l-gulonic acid was immovable at approximately 0.11 when a mixture of butanol, glacial acetic acid, and water was used as the developer.

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By catalytic reduction with PtO₂ as a catalyst in glacial acetic acid solution at ordinary temperature, dictamnine (I), isodictamnine (V), nordictamnine (VI), and skimmianine (IV) absorb 2 moles of hydrogen to yield C₁₂H₁₃NO₂, colorless silky needles, m.p. 186-187°, C₁₂H₁₃NO₂, long pillars, m.p. 185°, C₁₁H₁₁NO₂, prisms, m.p. 262° (monoacetate, white microneedles, m.p. 247-248°), and C₁₄H₁₇NO₄, prisms, m.p. 183°, repectively. The reduction product of (VI) was proved to be identical with 2, 4-dihydroxy-3-ethyl-quinoline, m.p. 262° (monoacetate, m.p. 248°), which was synthetically prepared from methyl N-butyrylanthranilate (pillars, m.p. 71°) by Camps' quinoline synthesis. The catalytic hydrogenation of 2, 3-furo-(2′, 3′)-quinoline compounds, therefore, causes the cleavage of the furan nucleus, producing 4-methoxy-2-hydroxy-3-ethylquinoline from (I), N-methyl-2-hydroxy-3-ethyl-γ-quinolone from (V), and 4, 7, 8-trimethoxy-2-hydroxy-3-ethylquinoline from (IV). Skimmianine used in this reduction was a sample isolated in 0.06% yield from the fresh leaves of Skimmia japonica Thunb. var. rugosa Yatabe. By the methylation of nordictamnine with diazomethane, dictamnine and isodictamnine were obtained in almost equal proportions.

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In the hope of finding compounds possessing analgesic properties, six compounds possessing the following general formula were prepared: The compounds were prepared by the oxidation of α-, β-, and γ-phenyl-N-methyl-piperidylcarbinols with a calculated amount of chromic acid in glacial acetic acid to α-, β-, and γ-benzoyl-N-methylpiperidines to which were applied phenyl- or 2-thienylmag-nesium bromide. The compounds synthesized are as follows:
R₁=R₂=phenyl, n=0, n′=4: Colorless prisms, m.p. 88.5-89.5°.
R₁=R₂=phenyl, n=1, n′=3: Colorless needles, m.p. 147-148°.
R₁=R₂=phenyl, n=2, n′=2: Colorless granules, m.p. 134-136°.
R₁=phenyl, R₂=2-thienyl, n=0, n′=4: Colorless needles, m.p. 93-94°.
R₁=phenyl, R₂=2-thienyl, n=1, n′=3: Colorless needles, m.p. 142-143°.
R₁=phenyl, R₂=2-thienyl, n=2, n′=2: Colorless rhombs, m.p. 147-148°.

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For the same reason, as of the previous paper, following three compounds possessing the same general formula were prepared by the application of 2-thienylmagnesium iodide to ethyl N-methylpiperidine-α-, β-, and γ-carboxylates.
R₁=R₂=2-thienyl, n=0, n′=4: Colorless prisms, m.p. 91-92.5°.
R₁=R₂=2-thienyl, n=1, n′=3: Colorless needles, m.p. 142°.
R₁=R₂=2-thienyl, n=2, n′=2: Colorless prisms, m.p. 161-163°.

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Heating of allithiamine (IV) in solvents of high boiling point, such as ethylene glycol and cyclohexanol, results in the formation of thiochrome (II), 3-[2′-methyl-4′-amino-pyrimidyl-(5′)]-methyl-4-methyl-5-β-hydroxyethylthiazole-2-thione (SB₁) (V), allyl mercaptan, and diallyl disulfide. The heating of (IV) in aqueous alkali solution results in the formation of allyl mercaptan, thiamine (VI), (II), and (V). In these cases, the formation of thiamine-thiazolone (III) was detected by the paper partition chromatography but it could not be isolated in a crystalline form.

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Because of a deep interest in the relationship between the chemical structure and pharmacological properties of emetine, a series of compounds possessing structures allied to the emetine structure, recently determined by Robinson, were prepared. Comparative examination of these compounds with natural emetine was carried out together with the examination of chemical properties. In the present paper, preparation of rac-C-bis(Nor)emetine which lacks the ethyl group in the 6-position of benzoquinolizine nucleus in emetine, is described. A bis-(amide), obtained by the selective bonding of lmole of methanetriacetic acid and 2 moles of veratrylamine, was taken as the fundamental material for skeletal formation. This amide was subjected to dehydration-cyclization to the imide, reduced to the corresponding piperidone compound, and the benzoquinolizin-ium salt formed by isoquinoline cyclization. Catalytic reduction of this salt yielded the objective compound.

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Bacteriostatic and fungistatic effects of α, β-unsaturated ketones, such as benzalacetone and dibenzalacetone, were tested. It was found that the benzalacetone series were more effective against fungi and that cinnamalacetone had one-quarter the efficacy of benzalacetone. This indicates that a parallel relationship exists between anthelmintic and fungistatic acitivities, similar to the facts pointed out by Baldwin on anthelmintic activity.

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The efficacy against Trichophyton interdigitale and Achorion Schoenleinii of furacin, guanofuracin, panazone, Z-furan, furyl esters, nitrofuryl esters, anilides, amides of furancarboxylic acid, and furylacrylic acid were tested. The esters were found to be the most effective, 5-nitrofuryl furoate being the best as it was effective up to 64, 000 dilution. The results of subculture showed that there were tendency of resistant strains forming easily. Furacin and guanofuracin were found to be almost ineffective which showed that there was an inverse relationship between bacteriostatic and fungistatic actions.

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Heloniopsis japonica Maxim. (=H. orientalis Koidz.) is a perennial herb of Liliaceae family that grows wild in various parts of Japan. It has never been used as home remedies and no studies have ever been made of its constituents. A kind of amorphous crude saponin was isolated from the whole plant, collected during the flowering season. Hydrolysis of the saponin or the methanolic extract of the plant with hydrochloric acid yielded a kind of sapogenin as white needles, m.p. 206-207°, which gave an acetate of m.p. 197-198°. The analytical values corresponded to formula C₂₇H₄₂O₃ for sapogenin, and C₂₉H₄₄O₄ for the acetate, from which it was assumed that the sapogenin was identical with diosgenin.

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Three kinds of crystalline substances were isolated by a chromatography using alumina from the fraction yielding oleandrin from the leaves of Nerium odorum Soland. These three substances were tentatively designated as Nerium D, E, and F, the two latter ones being identified as 16-desacetylanhydroöleandrin and 16-anhydrogitoxigenin which were formed respectively from oleandrin and oleandrigenin by the action of alumina. Nerium D was assumed to be a cardiac glycoside of digitalis-strophanthus type, but the structure still remains unknown.

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A fraction which causes definite proliferation of the pigeon crop gland was isolated from a mature human placenta. This fraction is similar in its action to anterior pituitary prolactin in that it causes proliferation of the mucous membrane of the crop gland, but is different from prolactin in that vacuoles are formed by the liquefaction of epithelial cells in the middle layer of pavement epithelial cells, and the groups of cells above this portion come off and collapse. This substance precipitates at three kinds of isoelectric points of pH 6.4-6.5, pH 5.4-5.6, and pH 5.8-6.3, of which the first precipitate shows the strongest effect. A substance which shows such proliferation action is also contained in immature human placenta (in second to fifth month of pregnancy), the placenta of two to three months showing the strongest action.

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Utilizing the fluorescence reaction characteristic to dehydroascorbic acid (DAA), paper chromatograms of DAA solutions of various pH were prepared and found that each of these showed characteristic developed images which fact was contrary to the publication of Partridge. By the examination of the paper chromatograms of DAA solution left to stand for some time, it was found that the opinions of Herbert and Zilva were more suitable than that of Ghosh or Rosenfeld. Total vitamin C content was detected from 26 kinds of natural substances, mostly foodstuff, by the paper chromatography utilizing the fluorescence reation.

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Malic acid, tartaric acid, and citric acid were found in the young stem of Polygonum Reynoutria Makino, which were collected in the vicinity of Minoo-machi, near Osaka.

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The alcoholic solution of rutin, containing sodium nitrite and alminium nitrate, gives red coloration when alkalized with sodium hydroxide. The intensity of coloration is proportional to the concentration of rutin and can colorimetrically be determined by the Pulfrich photometer. This method can also be utilized for separatory determination of rutin and quercetin, and for the determination of rutin in rutin preparations.

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